7CRG

Beta-strand-mediated dimeric formation of the extended Ig-like domains of human lamin A/C

Summary for 7CRG

• Entry DOI: 10.2210/pdb7crg/pdb
• Descriptor: Prelamin-A/C (2 entities in total)
• Functional Keywords: lamin a/c, ig-like domain, dimer, nuclear protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 51152.83

Authors

Ahn, J.,Ha, N.C. (deposition date: 2020-08-13, release date: 2021-08-25, Last modification date: 2023-11-29)

Primary citation

Ahn, J.,Lee, J.,Jeong, S.,Kang, S.M.,Park, B.J.,Ha, N.C.
Beta-strand-mediated dimeric formation of the Ig-like domains of human lamin A/C and B1.
Biochem.Biophys.Res.Commun., 550:191-196, 2021

PubMed Abstract: Lamins are nuclear intermediate filament proteins that play an essential role in maintaining the nuclear structure by forming a 3-D meshwork. Lamins consist of the N-terminal unstructured head, the coiled-coil rod domain, and the C-terminal tail, which is mostly unstructured except for the Ig-like domain. To date, the Ig-like domain has been characterized as a monomeric structure. Here, we determined the crystal structures of human lamin A/C, including the Ig-like domain and its N- and C-terminal flanking sequences. Interestingly, the structures showed a homodimer formed by beta-strand interactions between the N- and C-terminal flanking sequences. This interaction also provides a molecular implication for the creation of a 3-D meshwork between the 3.5-nm-thick filaments. Furthermore, we determined the crystal structure of the corresponding region of lamin B1. The structure showed a similar dimeric assembly, also formed by beta-strand interactions, albeit the intersubunit distance was much shorter. Since the Ig-like domain contains many genetic hotspots causing lamin-related diseases in lamin A/C, our findings will help understand the detailed assembly of lamins in a 3-D meshwork structure and lamin-related diseases at the molecular level.

PubMed: 33706103
DOI: 10.1016/j.bbrc.2021.02.102

Experimental method

X-RAY DIFFRACTION (1.8 Å)